Ceramides Bioproduction Engineering Service

Ceramides are essential lipids in human skin, crucial for maintaining the skin's barrier function and hydration. They are widely utilized in cosmetics and skincare. Industrial production faces significant challenges. Natural extraction and purification from yeast or plants is complex, costly, and low-yielding . Chemical synthesis often lacks the bioactive stereoconfiguration found in natural Ceramides and relies on toxic reagents, leading to products with inferior biological activity and safety concerns. The fundamental biosynthetic bottleneck is the Insufficient intracellular pool of sphingoid base precursors (e.g., Sphinganine or Phytosphingosine) in the microbial host, which limits the final Ceramide titer.

CD Biosynsis offers a comprehensive metabolic engineering solution, typically using engineered yeast or fungi (e.g., Pichia pastoris or S. cerevisiae) due to their native sphingolipid pathway. To overcome the precursor bottleneck, we implement Metabolic engineering of yeast/fungi to overexpress key enzymes like Serine Palmitoyltransferase (SPT) and Keto Reductase (KRS) . SPT is the first and rate-limiting enzyme in the sphingoid base pathway; its overexpression significantly boosts the flux from Serine and Palmitoyl-CoA to Phytosphingosine. To control the final product structure, we Introduce specific Acyltransferases to control the synthesis of desired ceramide subtypes (e.g., Ceramide NP) . By selecting and optimizing Ceramide Synthases (CerS) with defined chain-length specificity (e.g., C18), we can precisely control the N-acyl chain of the Ceramide product, ensuring high yield and high purity of the desired bioactive subtype.

Pain Points

Developing high-quality, cost-effective Ceramides production faces these key challenges:

• Low Yield from Extraction: Isolation from natural sources (e.g., yeast, rice bran) requires extensive lipid extraction and chromatography, which is complex, inefficient, and results in Low yield and high cost .
• Lack of Bioactive Purity in Chemical Synthesis: Chemical routes struggle to precisely control the stereochemistry at the C1 and C3 positions of the sphingoid base, often yielding a racemic mixture that lacks the bioactive stereoconfiguration of natural Ceramides.
• Limiting Sphingoid Base Precursors: The Ceramide pathway starts with Serine and Palmitoyl-CoA. The bottleneck is the low activity of the rate-limiting enzyme Serine Palmitoyltransferase (SPT), leading to an Insufficient intracellular pool of sphingoid base precursors .
• Difficult Subtype Control: There are many Ceramide subtypes (NP, AP, EOP). Microbial hosts often produce a mixture of these, making it difficult to target the synthesis of one desired subtype needed for specific commercial formulations.

A successful solution must ensure a massive supply of the sphingoid base precursor and provide precise control over the final acyl chain structure.

Solutions

CD Biosynsis utilizes advanced metabolic engineering to optimize Ceramides production in yeast/fungi:

Overexpress Key Enzymes (SPT, KRS) to Boost Sphingoid Base Supply

           

We overexpress the rate-limiting enzymes (SPT, KRS) to exponentially increase the internal pool of the sphinganine precursor, resolving the Insufficient precursor pool issue.

Introduce Specific Acyltransferases for Ceramide Subtype Control (Ceramide NP)

We introduce a Ceramide Synthase (CerS) with C18 or C 24 acyl chain specificity to direct the formation of a single, high-purity Ceramide subtype (NP or AP).

Block Competitive Lipid Pathways

We use gene knockouts (e.g., Tsc3 or Sur 2 genes in yeast) to prevent precursor conversion into less desired complex sphingolipids or glycolipids.

Optimize Fatty Acid Chain Pool

We engineer the fatty acid elongation system (Elovl genes) to ensure the optimal long-chain fatty acyl-CoA is available for the Ceramide Synthase to use.

This systematic approach increases production yield while ensuring the final product is a single, highly active Ceramide subtype.

Advantages

Our Ceramides engineering service is dedicated to pursuing the following production goals:

High Titer and Yield

Overexpression of SPT effectively eliminates the rate-limiting step, leading to commercially viable, high Ceramide titers, overcoming low yield .

High Stereoconfigurational Purity

Enzymatic biosynthesis inherently controls the stereochemistry of the sphingoid base, guaranteeing the bioactive natural form , unlike chemical synthesis.

Targeted Subtype Production Icon

CerS selection allows the production of a single, specific Ceramide subtype (e.g., NP), offering higher purity and value for formulation. [Image of Cost Reduction Icon]

Biocompatible and Safe Icon

The microbial host ensures the product is free from animal-derived components and toxic chemical reagents used in synthesis.

Simplified Extraction Icon

Focusing production on simple Ceramides (versus complex glycolipids) simplifies the final lipid extraction and purification process.

We provide a reliable, high-quality, and high-purity source for bioactive Ceramides.

Process

Our Ceramides strain engineering service follows a rigorous, multi-stage research workflow:

• Precursor Pathway Boosting: Overexpress the Serine Palmitoyltransferase (SPT and Tsc3 genes) and Keto Reductase (KRS) to maximize the production of sphinganine.
• Targeted Acylation: Introduce a heterologous Ceramide Synthase (CerS) with the desired acyl chain specificity (e.g., CerS 2 for C 24 Ceramides) to form the final Ceramide subtype.
• Competing Pathway Blockade: Knockout genes responsible for complex sphingolipid synthesis (e.g., sphingolipid desaturases and transferases) to prevent product diversion.
• Fatty Acid Chain Tuning: Engineer fatty acid elongase genes (Elovl) to ensure sufficient supply of the acyl-CoA chain needed by the introduced CerS.
• Titer and Purity Validation: Validate the engineered strain in fed-batch culture, measuring the final total Ceramide titer (g/L) and the purity of the targeted Ceramide subtype (HPLC and LC-MS).

Technical communication is maintained throughout the process, focusing on timely feedback regarding yield and product quality attributes.

Explore the potential for a high-titer, high-purity Ceramides supply. CD Biosynsis provides customized strain and process engineering solutions:

• Detailed Sphingoid Base Precursor Concentration Report , demonstrating the effect of SPT overexpression.
• Consultation on optimized lipid extraction and purification protocols for the high-yield Ceramide product.
• Experimental reports include complete raw data on total Ceramide titer, yield, and final Ceramide subtype composition , crucial for cosmetic and medical formulation.